Objective-As the initiation and acceleration of alcohol use commonly occurs during adolescence, the etiological basis for this phenomenon is of critical importance. Using the diathesis-stress model as a framework, this review will evaluate the emerging evidence implicating the limbic-hypothalamic-pituitary-adrenal (LHPA) axis in the development of alcohol use disorder (AUD).Method-Searches were conducted of the PubMed/Medline, PsycInfo, PsycBooks, Cochrane and ISI Web of Science databases, using a specified set of search terms.Results-Genetic liabilities, antenatal stress/anxiety or exposure to addictive substances, exposure to maltreatment or other traumatic events in childhood and psychiatric illness in childhood/adolescence can all increase the risk, or diathesis, for AUD. Greater LHPA dysfunction may serve as a marker for higher diathesis levels in youth. When exposed to stressors in adolescence, high-risk youth (or those with greater LHPA dysfunction) may use alcohol and/or other substances to cope with stressors and, in turn, become more vulnerable to AUD.Conclusion-Evidence suggests that LHPA dysfunction and stress play an important role in the development of AUD. Genetic liabilities, antenatal insults, maltreatment and psychiatric illness appear to increase LHPA dysfunction, raising risk for AUD. Further research is needed to clarify the complex interplay among adverse developmental experiences, LHPA dysfunction and the development of AUD in adolescents.

Anxiety experienced in anticipation of impending aversive events induces striatal-limbic activation. However, previous functional magnetic imaging (fMRI) studies of anticipatory anxiety have utilized post-test measures of anxiety, making a direct association between neural activation and distress problematic. This paradigm was designed to assess the BOLD response to an aversive conditioned stimulus while simultaneously measuring subjective anxiety. Fifteen male healthy subjects (45.5±8.5 years old) were studied. A high threat conditioned stimulus (CS) was paired with either an unpredictable, highly aversive (painful) or a non-aversive (non-painful) unconditioned stimulus and compared to a low threat CS paired with a predictable, non-aversive stimulus. Neural response was assessed with fMRI, and subjective anxiety (1 to 4) was recorded upon the presentation of each CS. High subjective ratings of real-time anticipatory anxiety (2, 3, and 4), relative to low anticipatory anxiety (1), elicited increased activation in the bilateral striatum, bilateral orbital frontal cortex, left anterior insula, and anterior cingulate cortex (ACC) and decreased activation in the posterior cingulate cortex (PCC). The amplitude of BOLD signal change generally paralleled the subjective rating of anxiety. Real-time measures of anticipatory anxiety confirm previous reports, using post-test measures of anxiety, of striatal-limbic activation during anticipatory anxiety while simultaneously demonstrating an increase in BOLD response in parallel with heightened anxiety.

A design change that reduced the openness of the unit resulted in the reduction of seclusion and restraint.